Cholesterol side-chain cleavage and 11 beta-hydroxylation are inhibited by gossypol in adrenal cortex mitochondria.
Cholesterol side-chain cleavage and 11 beta-hydroxylation were assessed in isolated adrenal cortex mitochondria by formation of pregnenolone and corticosterone, respectively, in the presence and absence of gossypol. Pregnenolone biosynthesis was inhibited when increasing concentrations of gossypol were added. The control value of 4 nmol min-1 mg-1 dropped to 2 nmol min-1 mg-1 with 30 microM of the drug in the incubation medium. A more pronounced inhibitory effect was observed upon 11 beta-hydroxylation of steroids; I50 was 11 microM. Seventy-five percent of corticosterone production was impaired when 30 microM of gossypol were present. Bovine serum albumin prevented and reversed the inhibitory action of the drug. Kinetic studies showed a linear mixed type inhibition, suggesting a direct action of the drug upon the enzymatic complex. This study demonstrates a direct inhibitory effect of gossypol upon the steroidogenic enzymes located in the inner mitochondrial membrane of the adrenal cortex.
Cuéllar
A
A
Departamento de Bioquimica, Instituto Nacional de Cardiologia Ignacio Chávez, México City, México.
Diaz-Sánchez
V
V
Ramírez
J
J
D000302:Adrenal Cortex / Q000201:enzymology* / Q000648:ultrastructure; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors*; D003345:Corticosterone / Q000096:biosynthesis; D004285:Dogs; D006072:Gossypol / Q000494:pharmacology*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D011284:Pregnenolone / Q000096:biosynthesis; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors*
D011284:Pregnenolone; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006072:Gossypol; D003345:Corticosterone